Bone Marrow Cells in Murine Colitis: Multi-Signal Analysis Confirms Pericryptal Myofibroblast Engraftment without Epithelial Involvement

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P27Kip1, regulated by glycogen synthase kinase-3β, results in HMBA-induced differentiation of human gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is the second most common cause of global cancer-related mortality. Although dedifferentiation predicts poor prognosis in gastric cancer, the molecular mechanism underlying dedifferentiation, which could provide fundamental insights into tumor development and progression, has yet to be elucidated. Furthermore, the molecular mechanism underlying the effects of hexamethylene bisacetamide (HMBA), a recently discovered differentiation inducer, requires investigation and there are no reported studies concerning the effect of HMBA on gastric cancer.</p> <p>Methods</p> <p>Based on the results of FACS analysis, the levels of proteins involved in the cell cycle or apoptosis were determined using western blotting after single treatments and sequential combinations of HMBA and LiCl. GSK-3β and proton pump were investigated by western blotting after up-regulating Akt expression by Ad-Akt infection. To investigate the effects of HMBA on protein localization and the activities of GSK-3β, CDK2 and CDK4, kinase assays, immunoprecipitation and western blotting were performed. In addition, northern blotting and RNase protection assays were carried out to determine the functional concentration of HMBA.</p> <p>Results</p> <p>HMBA increased p27Kip1 expression and induced cell cycle arrest associated with gastric epithelial cell differentiation. In addition, treating gastric-derived cells with HMBA induced G0/G1 arrest and up-regulation of the proton pump, a marker of gastric cancer differentiation. Moreover, treatment with HMBA increased the expression and activity of GSK-3β in the nucleus but not the cytosol. HMBA decreased CDK2 activity and induced p27Kip1 expression, which could be rescued by inhibition of GSK-3β. Furthermore, HMBA increased p27Kip1 binding to CDK2, and this was abolished by GSK-3β inhibition.</p> <p>Conclusions</p> <p>The results presented herein suggest that GSK-3β functions by regulating p27Kip1 assembly with CDK2, thereby playing a critical role in G0/G1 arrest associated with HMBA-induced gastric epithelial cell differentiation.</p

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field

In situ impacts of a flooding event on contaminant deposition and fate in a riparian ecosystem

Purpose: Floodwaters contain a mixture of organic contaminants which affect both the water and soil quality within flooded regions. This study is the first to describe the chemical behavior of organic contaminants mobilized during the 2010 flooding event of the Rio Grande. The study compares two sites: one directly impacted by outfall from municipal sources and one primarily impacted by rural runoff. Materials and methods: This study characterized the in situ cycling of organic contaminants (triclosan, ciprofloxacin, and atrazine), their depositional mechanisms, and the post-flood dynamics within riparian soils over 6 months. Water quality (pH, salinity, alkalinity, turbidity, N, and P) of the Rio Grande at four sites within Webb County, TX, was monitored for 3 months pre-flooding and 6 months post-flooding in order to determine contaminant levels along the Webb County border. Soil physicochemical properties (pH, CEC, and EC) were assessed for 6 months at two sites post-flooding: within the municipal area of both Laredo, TX, USA, and Nuevo Laredo, Mexico (LCC site), and upstream of the site near the edge of Laredo, TX (MR site). Results and discussion: Low levels of contaminants were detected in the watershed year-round with levels increasing during the flood. Floodwaters had a lower pH than nonflooding conditions, resulting in greater partitioning of both triclosan and ciprofloxacin to particles within the water column with no change detected in atrazine behavior. Soil samples (0–2-cm depth) showed an increase in clay-sized particles (up to 6–14 %) and contaminant concentrations similar to that of water column particles. Organic contaminants were uniform in concentration throughout the soil profile (2–30 cm), demonstrating the impact of infiltration. Both triclosan and atrazine decayed away at rates of 23 ± 2 and 16 ± 1 days, respectively, with no decay of ciprofloxacin detected. Vertical mobility of contaminants within soils was not detected. Conclusions: This study was able to distinguish the influx of contamination contributed by particle deposition from that due to infiltration of the contaminated floodwaters. Further, our data indicates that outfall/effluent contaminants, such as ciprofloxacin, may persist in riparian soils post-flooding. Agricultural management should consider potential exposure and accumulation of floodwater contaminants in crops

Fate of triclosan in irrigated soil: Degradation in soil and translocation into onion and tomato

This study determined the fate of triclosan, a prevalent wastewater contaminant in recycled waters and surface streams, when soil and crop plants were irrigated at environmentally relevant concentrations. Soil triclosan concentrations were monitored in an 8-wk and in a 16-wk study without plants to determine triclosan degradation. Onion (Allium oschaninii O. Fedtsch.) and tomato (Solanum lycopersicum L.) were assessed for growth and triclosan accumulation at four levels of triclosan exposure (0, 0.015, 0.15, and 1.5 μg L-1) in irrigation waters within ranges of those found in recycled waters and associated receiving streams. Onions were grown for 8 wk and tomatoes were grown for 8 wk (short-term study) and 12 wk (long-term study) in potting soil. Soil triclosan concentrations increased (5-fold) with triclosan levels applied to soils alone. With repeated application, the half-life of triclosan was 18 d, with low-level accumulation in soil. Bioaccumulation of triclosan was observed in all edible portions of onions (115-435 ng g-1), primarily in bulbs, with no discernible impact on biomass. In both short- and long-term tomato studies, triclosan translocated to shoots and fruits (approaching a translocation factor of 1) at the highest level examined. Even at low triclosan concentrations typically found in recycled waters and receiving streams, agricultural irrigation presents an additional exposure route for organic contaminants to humans via commercial crops. Our study indicates that bulb crops, in particular, would likely accumulate high levels of triclosan. However, concentrations detected in both onions and tomato fruits determined here are below current human exposure limits

Temporal trends of triclosan contamination in dated sediment cores from four urbanized estuaries: Evidence of preservation and accumulation

Triclosan is an antimicrobial agent added to a wide array of consumer goods and personal care products. Through its use, it is introduced into municipal sewer systems where it is only partially removed during wastewater treatment. In this study, triclosan was measured in dated sediment cores from four urbanized estuaries in order to reconstruct temporal and spatial trends of accumulation. Measurable concentrations of triclosan first appeared in each of the sediment cores near 1964, which corresponds with the US patent issuance date of triclosan. The presence of triclosan at each of the study sites at or near the patent date indicates that long-term preservation is occurring in estuarine sediments. Temporal trends of triclosan at each location are unique, reflecting between site variability. Concentrations at one site climbed to as high as 400 ng g-1, due in part, to local commercial production of triclosan. At two locations, levels of triclosan rise towards the surface of each core, suggesting increasing usage in recent years. One location adjacent to a major combined sewer overflow had high sediment concentrations of triclosan, confirming their potential as a source of triclosan to estuaries

Downhill from devaluation: The battle for sterling, 1967–1972

The devaluation of 1967 and the float of 1972 have become two of the key cornerstones in the analysis of sterling under the Bretton Woods system. Sterling’s fortunes between 1968 and 1972 have not been so well documented. This article uncovers new evidence about the pound for this period, including the British government’s contingency plans for blocking the sterling balances as a means to negate the weakness of sterling following the 1967 devaluation, the discussions with the United States on the reform of the international monetary system, and the preparations made for floating the pound